Butanol is one of the most promising biofuels with many advantages over bioethanol, and it has been used in large-scale processes over the last decades. Butanol plant using technology of butanal hydrogenation by using three reactors in the series. This study was aimed to simulate butanol production from hydrogenation of butanal by using Aspen Plus. The simulation was performed to evaluate the impact of by-passing the second liquid phase reactor in the series due to the catalyst blockage problem leading to the plant shutdown. The attested model was subsequently used to simulate butanal hydrogenation at different reactor configuration, reactor operating conditions and reactor size.